Macrophage-derived matrix metalloproteinase-1 enhances aortic aneurysm formation in transgenic rabbits

Increased expression of matrix metalloproteinase-1(MMP-1)has been observed in the lesions of atherosclerosis and aneurysms;however,it is not fully understood whether macrophage-derived MMP-1 affects these diseases.To investigate whether macrophage-derived MMP-1 participates in the development of vascular diseases,we generated transgenic(Tg)rabbits expressing human MMP-1 in the monocyte/macrophage lineage under the control of the human scavenger receptor enhancer/promoter.Tg rabbits exhibited no visible abnormalities throughout their bodies.Western blotting analysis revealed that the amount of MMP-1 proteins in the conditioned media secreted from peritoneal macrophages of Tg rabbits was up to 3-fold higher than that in non-Tg rabbits.For the first experiment,Tg and non-Tg rabbits were fed a cholesterol diet for 16 weeks,and aortic and coronary atherosclerosis were evaluated.The gross lesion area of aortic atherosclerosis in Tg rabbits was not significantly different from that in non-Tg rabbits,but Tg rabbits had marked destruction of the medial elastic lamina of the aortic lesions on microscopic examination.For the second experiment,we generated aortic aneurysms by incubating with elastase.Compared with non-Tg rabbits,Tg rabbits exhibited a significantly greater aortic dilation.Increased macrophage-derived MMP-1 led to increased medial destruction in both aortic atherosclerosis and aneurysms.These results demonstrate that MMP-1 plays a different role in the pathogenesis of atherosclerosis and aneurysms.

Levels of matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 in gastric cancer

AIM:To evaluate the levels of preoperative serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in gastric cancer.METHODS:One hundred gastric cancer patients who underwent gastrectomy were enrolled in this study.The serum concentrations of MMP-1 and TIMP-1 in these patients and in fifty healthy controls were determined using an enzyme-linked immunosorbent assay.RESULTS:Higher serum MMP-1 and TIMP-1 levels were observed in patients than in controls (P < 0.001).Serum MMP-1 and TIMP-1 levels were positively associated with morphological appearance,tumor size,depth of wall invasion,lymph node metastasis,liver metastasis,perineural invasion,and pathological stage.They were not significantly associated with age,gender,tumor location,or histological type.CONCLUSION:Increased MMP-1 and TIMP-1 were associated with gastric cancer.Although these markers are not good markers for diagnosis,these markers show in advanced gastric cancer.

Expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in ulcerative colitis

AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polymerase chain re- action (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and TIMP-1 at both mRNA and protein levels in patients with UC and con- trols. The relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and the sever- ity of clinical symptoms of the patients with UC were also analyzed. RESULTS: The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and inflamed colonic mucosa was signifi cantly higher than that in the non-inflamed colonic mucosa (P < 0.001), but there was no statistically signif i- cant difference in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05). The mRNA ex- pression of MMP-1 and TIMP-1 in ulcerated colonic mu- cosa of UC patients was increased by 80-fold and 2.2-fold, respectively when compared with the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and 1.6-fold, respectively. Immunohistochemical analy- sis showed that among the ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35% respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and 75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical symptoms (P <0.05).CONCLUSION: Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC pa-tients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/ TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC.

Expression of matrix metalloproteinase-1 and tumor necrosis factor-α in ulcerative colitis

AIM: To examine the expression of matrix metallo-proteinase-1 (MMP-1) and tumor necrosis factor-α (TNF-α) in the colon mucosa of patients with ulcerative colitis (UC). METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to examine the expression of MMP-1 and TNF-α at both mRNA and protein levels in the colon mucosa of patients with UC. Correlation between MMP-1 and TNF-α and their correlation with the severity of the disease were also analyzed statistically. RESULTS: The expression of MMP-1 and TNF-α in the ulcerated and inflamed colon mucosa of patients with UC was significantly higher than that in the non-inflamed mucosa of normal controls at both mRNA and protein levels. Furthermore, the expression of MMP-1 and TNF-α in the ulcerated area was significantly higher than that in the inflamed area of patients with UC (0.9797 ± 0.1433 vs 0.6746 ± 0.0373, 0.8669 ± 0.0746 vs 0.5227 ± 0.0435, P < 0.05). There was no statistically significant difference in the non-inflamed area of normal controls. There was a significant correlation between MMP-1 and TNF-α expression (0.9797 ± 0.1433 vs 0.8669 ± 0.0746, P < 0.05), the correlating factor was 0.877. MMP-1 and TNF-α showed a significant correlation with the severity of the disease (0.0915 ± 0.0044 vs 0.0749 ± 0.0032 , 0.0932 ± 0.0019 vs 0.0724 ± 0.0043, P < 0.05), their correlating factors were 0.942 and 0.890, respectively. CONCLUSION: Excessively expressed MMP-1 directly damages the colon mucosa by degrading extracellular matrix (ECM) in patients with UC. While damaging colon mucosa, excessively expressed TNF-α stimulates MMPs secreting cells to produce more MMP-1 and aggravates the mucosa damage. MMP-1 promotes secretion ofTNF-α in a positive feedback manner to cause further injury in the colon mucosa. MMP-1 and TNF-α correlate well with the severity of the disease, and therefore, can be used clinically as biological markers to judge the severity of UC.

Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.

肝细胞癌患者血清ECM1、MMP-9和VEGF水平的变化及其意义

目的 探究肝细胞癌患者血清细胞外基质蛋白-1(ECM1)、基质金属蛋白酶-9(MMP-9和血管内皮生长因子(VEGF)水平的变化及其意义。方法 对60例肝细胞癌患者进行回顾性分析,患者主要使用甲磺酸阿帕替尼进行治疗,必要时也可联合GEMOX方案肝动脉化疗栓塞术进行治疗。采用酶联免疫吸附法测定患者治疗前后的血清ECM1、VEGF、MMP-9水平。比较患者治疗前后ECM1、MMP-9和VEGF水平;比较不同临床病理特征(年龄、性别、血管侵犯、淋巴结转移、TNM分期、Edmondson分期和肿瘤直径)患者ECM1、MMP-9和VEGF水平。结果 治疗后,患者ECM1、MMP-9以及VEGF水平分别为(135.23±44.58)pg/ml、(421.25±87.56)μg/L和(657.56±54.56)pg/ml,均低于治疗前的(215.56±30.80)pg/ml、(499.56±30.56)μg/L、(798.02±50.79)pg/ml(P<0.05)。不同年龄、性别患者ECM1、MMP-9、VEGF水平比较差异无统计学意义(P>0.05);不同血管侵犯、淋巴结转移、TNM分期、Edmondson分期和肿瘤直径患者ECM1、MMP-9、VEGF水平比较差异具有统计学意义(P<0.05)。结论 ECM1、MMP-9、VEGF三者相互作用可促进肝癌细胞的转移,可根据其水平情况,了解患者肝细胞、肝功能健康状况。

血清NY-ESO-1自身抗体和MMP1联合检测对食管鳞状细胞癌的诊断价值

目的:探讨血清基质金属蛋白酶-1(matrix metalloproteinase-1,MMP1)和纽约食管鳞状细胞癌抗原-1(New York esophageal squamous cell carcinoma 1,NY-ESO-1)自身抗体联合检测在食管鳞状细胞癌中的诊断意义。方法:应用酶联免疫吸附实验检测120例食管鳞状细胞癌患者和120例正常对照血清中MMP1和NY-ESO-1自身抗体的表达水平,采用受试者工作特征(receiver operating characteristic,ROC)曲线评价诊断效能。结果:血清MMP1和NY-ESO-1自身抗体在食管鳞状细胞癌患者中的表达均明显高于正常对照[(8.070±5.738)ng/mL vs(4.331±3.137)ng/mL,Z=6.214,P<0.001;0.463±0.571 vs 0.156±0.086,Z=5.210,P<0.001]。ROC曲线显示,当血清MMP1为最佳诊断临界值10.586 ng/mL时,其在诊断食管鳞状细胞癌的曲线下面积(area under the ROC curve,AUC)为0.732(95%CI:0.671~0.787),敏感度为24.2%,特异度为95.0%。NY-ESO-1自身抗体诊断食管鳞状细胞癌AUC为0.695(95%CI:0.632~0.752),敏感度为33.0%,特异度为95.0%。MMP1和NY-ESO-1自身抗体联合检测诊断食管鳞状细胞癌的AUC为0.800(95%CI:0.744~0.849),敏感度为47.5%,特异度为95.0%。结论:血清MMP1和NY-ESO-1自身抗体联合检测可能有助于提高食管鳞状细胞癌的诊断效能。

EGR-1和MMP-2在早期自然流产患者中的表达及临床意义

目的探讨早期生长反应因子(EGR-1)和基质金属蛋白酶-2(MMP-2)在早期自然流产患者绒毛中的表达及临床意义。方法采用RT-PCR和Westernblot检测20例早期自然流产患者(流产组)和20例正常早孕人工流产(对照组)绒毛组织中EGR-1和MMP-2的表达情况。结果流产组中EGR-1、MMP-2 mRNA和蛋白水平明显低于对照组,差异有统计学意义(P<0.05)。结论EGR-1和MMP-2在早孕绒毛组织中表达异常可能参与早期妊娠失败的发生。

慢性肾脏病患者血清CHI3L1、MMP-13表达水平及其病情评估、预后价值

目的探讨慢性肾脏病患者血清几丁质酶3样蛋白1(CHI3L1)、基质金属蛋白酶-13(MMP-13)表达水平及病情评估、预后价值。方法选取2020年3月至2022年8月在江油市人民医院就诊的208例慢性肾脏病患者作为病例组,按照病情严重程度将208例慢性肾脏病患者分为Ⅰ期组21例、Ⅱ期组42例、Ⅲ期组86例、Ⅳ期组38例、Ⅴ期组21例。另选取同期152例体检健康者作为对照组。根据患者预后情况将208例患者分为预后良好组(n=92)及预后不良组(n=116)。收集受试人员一般资料,采用酶联免疫吸附试验检测血清CHI3L1、MMP-13表达水平,Pearson法分析慢性肾脏病患者血清CHI3L1、MMP-13表达水平的相关性,以及二者与肾小球滤过率(GFR)的相关性,采用Cox回归分析影响慢性肾脏病患者预后的因素。结果对照组、病例组年龄、性别等一般资料比较,差异无统计学意义(P>0.05);病例组患者血清中CHI3L1表达水平较对照组显著增加,但MMP-13表达水平显著降低,差异有统计学意义(P<0.05);随着病情分期增加,患者血清CHI3L1表达水平随之增加,MMP-13表达水平随之降低(P<0.05);预后不良组患者血清CHI3L1表达水平较预后良好组显著增加,MMP-13表达水平显著降低(P<0.05);Pearson法分析显示,慢性肾脏病患者血清CHI3L1、MMP-13表达水平呈负相关,CHI3L1表达水平与GFR呈负相关,MMP-13表达水平与GFR呈正相关(P<0.05)。Cox回归分析显示,血清CHI3L1、MMP-13、GFR为慢性肾脏病患者预后不良的独立影响因素(P<0.05)。结论慢性肾脏病患者血清CHI3L1表达水平升高,MMP-13表达水平降低,二者均可用于病情及预后评估。

3D打印技术用于经鼻蝶窦入路垂体腺瘤切除术应用效果及对血清MMP-9和IGF-1水平的影响

目的:探究3D打印技术在经鼻蝶窦入路垂体腺瘤(PA)切除术的应用效果及对血清基质金属蛋白酶-9(MMP-9)和胰岛素样生长因子-1(IGF-1)水平的影响。方法:选取2020年5月至2022年5月秦皇岛市第一医院收治的84例PA患者,按照随机数表法将其分为观察组和对照组,每组42例。对照组行经鼻蝶窦入路垂体腺瘤切除术,观察组行经鼻蝶窦入路垂体腺瘤切除术联合应用3D打印技术,比较两组肿瘤切除效果、围术期指标、视力改善情况、MMP-9和IGF-1水平,以及鼻腔功能的鼻气道阻力(NAR)、T&T嗅觉测试评分及并发症。结果:观察组肿瘤切除效果优于对照组,差异有统计学意义(U=2.286,P<0.05);观察组手术时间、术中出血量及住院时间均少于对照组,差异有统计学意义(t=4.780、11.438、11.842,P<0.05);术后3 d、7 d时观察组血清MMP-9和IGF-1水平低于对照组,差异有统计学意义(F=7.526、4.985,P<0.05);术后1个月、3个月时观察组NAR及T&T嗅觉测试评分低于对照组,差异有统计学意义(F=6.359、8.436,P<0.05);两组视力视野改善情况及并发症发生率比较,差异无统计学意义(P>0.05)。结论:3D打印技术用于经鼻蝶窦入路垂体腺瘤切除术可提高肿瘤切除效果,优化手术操作,减少创伤,有利于减轻疼痛,改善嗅觉功能与视力视野,并能降低血清MMP-9、IGF-1水平,且安全性较高。

MMP-9与IGF-1在垂体腺瘤患者中的表达及其临床预测价值

目的探究MMP-9与IGF-1在垂体腺瘤患者中的表达及其临床预测价值。方法回顾性分析84例垂体腺瘤患者临床资料,分析不同病理垂体腺瘤患者的血清指标[基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、胰岛素样生长因子-1(insulin-like growth factor 1,IGF-1)]水平差异。84例垂体腺瘤患者依据治疗后肿瘤直径大小和转移率分为缓解组(n=40)与未缓解组(n=44),采用受试者工作特征(ROC)曲线分析MMP-9、IGF-1对垂体腺瘤患者预后的评估效能。结果不同肿瘤直径的垂体腺瘤患者MMP-9、IGF-1水平比较无显著性差异(P>0.05);未发生淋巴结转移的患者MMP-9水平明显低于发生转移的患者,而IGF-1水平高于发生转移的患者,差异有统计学意义(P<0.05);临床分期为Ⅰ~Ⅱ期的垂体腺瘤患者MMP-9水平明显低于Ⅲ~Ⅳ期患者,而IGF-1水平高于Ⅲ~Ⅳ期患者,差异有统计学意义(P<0.05)。缓解组患者MMP-9低于同期未缓解组,IGF-1水平明显高于同期未缓解组患者,差异有统计学意义(P<0.05)。ROC曲线结果显示血清中MMP-9与IGF-1的截断值分别为16.61 ng/L、229.06 ng/L,MMP-9预测ROC曲线下面积(AUC)为0.871(95%CI=0.778~0.935),敏感度75.61%,特异度92.50%,IGF-1预测ROC曲线AUC为0.851(95%CI=0.755~0.921),敏感度75.61%,特异度87.50%。结论血清中MMP-9,IGF-1水平与垂体腺瘤患者临床病理特征及预后情况密切相关,可通过早期检测结果进一步优化诊治措施。

Madecassoside impedes invasion of rheumatoid fibroblast-like synoviocyte from adjuvant arthritis rats via inhibition of NF-κB-mediated matrix metalloproteinase-13 expression

Fibroblast-like synoviocytes(FLS) play a pivotal role in Rheumatoid arthritis(RA) pathogenesis through aggressive migration and invasion. Madecassoside(Madec), a triterpenoid saponin present in Centella asiatica herbs, has a potent anti-inflammatory effect. In the present study, Madec exerted an obvious therapeutic effect in reversing the histological lesions in adjuvant-induced arthritis(AIA) rats. To recognize the anti-rheumatoid potentials of Madec, we further investigated whether Madec interfered with FLS invasion and metalloproteinase(MMP) expression. In cultures of primary FLS isolated from the AIA rats, Madec(10 and 30 μmol·L–1) was proven to considerably inhibit migration and invasion of FLS induced by interleukin 1β(IL-1β), but exhibiting no obvious effect on cell proliferation. Madec repressed IL-1β-triggered FLS invasion by prohibiting the expression of MMP-13. Additionally, Madec suppressed MMP-13 transcription via inhibiting the MMP-13 promoter-binding activity of NF-κB. Our results further showed that Madec down-regulated the translocation and phosphorylation of NF-κB as demonstrated by Western blotting and immunofluorescence assays. In conclusion, our results suggest that Madec exerts anti-RA activity via inhibiting the NF-κB/MMP-13 pathway.

Methanol extract of Codium fragile inhibits tumor necrosis factor-ɑ-induced matrix metalloproteinase-9 and invasiveness of MDA-MB-231 cells by suppressing nuclear factor-κB activation

Objective:To evaluate whether the methanol extract of Codium fragile(MECF) regulates tumor necrosis factor-α(TNF-α)-induced invasion of human breast cancer MDA-MB-231 cells by suppressing matrix metalloproteinase-9(MMP-9).Methods:Reverse transcriptionpolymerase chain reaction(RT-PCR) and western blot analysis were performed to analyze the expression of MMP-9 and nuclear factor-κB(NF-κB) subunits,p65 and p50,and IκB in MDA-MB-231 cells.3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide(MTT) assay was used for cell viability.MMP-9 activity and invasion were measured by gelatin zymography and a matrigel invasion assay,respectively.NF- κB activity was measured by an electrophoretic mobility shift assay and luciferase activity.Results:MECF had no effects on cell viability up to a concentration of 100 μg/mL in human breast cancer MDA-MB-231 cells regardless of the presence of TNF-α.MDA-MB-231 cells that were stimulated with TNF-α showed a marked increase of invasion compared to the untreated control,whereas pretreatment with MECF downregulated the TNF-α-induced invasion of MDA-MB-231 cells.Additionally,zymography,western blot analysis,and reverse transcriptase-polymerase chain reaction(RT-PCR) confirmed that MECF decreased TNF-α-induced MMP-9 expression and activity which is a key regulator for cancer invasion.According to an electrophoretic morbidity shift assay,pretreatment with MECF in MDA-MB-231 cells significantly decreased the TNF-α-induced DNA-binding activity of nuclear factor- κB(NF- κB),which is an important transcription factor for regulating cancer invasion-related genes such as MMP-9.Furthermore,treatment with MECF sustained the expression of p65 and p50 in response to TNF-α in the cytosolic compartment.The luciferase assay demonstrated that MECF attenuated TNF-α-induced NF- κB luciferase activity.Conclusion:MECF exhibited its antiinvasive capability by downregulating TNF-α-induced MMP-9 expression,resulting from the suppression of NF- κB activity in the human breast cancer cell line MDA-MB-231.

Salvia miltiorrhiza-asarum ointment combined with Chinese medical massage alleviates symptoms of osteoarthritis in a rat model through the Notch1/matrix metalloproteinase-13 signaling pathway

OBJECTIVE:This study investigated the effect of salvia miltiorrhiza-asarum ointment(SMAO)plus Chinese medical massage on knee osteoarthritis in a rat model.METHODS:Hulth's method was used to establish a Sprague-Dawley rat model of knee osteoarthritis(OA).The levels of matrix metalloproteinase-13(MMP-13),collagen-Ⅱ,aggrecan,interleukin(IL)-1β,tumor necrosis factor-α(TNF-α),and IL-6 were measured by enzyme-linked immunosorbent assays.The joint space was assessed by a Perlove X-ray system.Histopathology was examined by hematoxylin-eosin and Safranin O staining.The mRNA and protein expression levels of Notch1,MMP-13,collagen-Ⅱ,and aggrecan were measured by quantitative reverse transcription-polymerase chain reaction and Western blotting,respectively.RESULTS:SMAO plus Chinese medical massage significantly decreased the levels of MMP-13,IL-1β,TNF-α,and IL-6,and increased serum collagen-Ⅱ and aggrecan levels.Pathological injury of the knee joint was improved by SMAO treatment.mRNA and protein expression of Notch1 and MMP-13 was remarkably downregulated,but collagen-Ⅱ and aggrecan levels were significantly upregulated in cartilage tissues.CONCLUSION:SMAO combined with Chinese medical massage effectively relieves OA symptoms,which may involve inhibiting inflammation through the Notch1/MMP-13 signaling pathway.

Effects of (-)-epigallocatechin-3-gallate on expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in fibroblasts irradiated with ultraviolet A

Background It is known that ultraviolet irradiation can affect cellular function through a number of signaling pathways ( ) epigallocatechin 3 gallate (EGCG) is the major effective component in green tea and can offer protection from ultraviolet induced damage In this study, we investigated the protective mechanism of EGCG on human dermal fibroblasts damaged by ultraviolet A (UVA) in vitro Methods Transcription factor Jun protein levels were measured by Western blot Matrix metalloproteinase 1 (MMP 1) and tissue inhibitor of metalloproteinase 1 (TIMP 1) mRNA were studied by reverse transcription polymerase chain reaction (RT PCR) analysis in conjunction with computer assisted image analysis MMP 1 and TIMP 1 proteins were quantified by enzyme linked immunosorbent assay (ELISA) Results EGCG decreased transcription activity of Jun protein after induction by UVA Both the mRNA and protein levels of MMP 1 were increased by UVA irradiation, while no significant changes were observed in TIMP 1 levels The ratio of MMP 1 to TIMP 1 showed statistically significant differences compared with the control EGCG decreased the ratio of MMP 1 to TIMP 1 by inhibiting UVA induced MMP 1 expression ( P <0 05) Conclusion EGCG can protect human fibroblasts against UVA damage by downregulating the transcription activity of Jun protein and the expression of MMP 1 The ratio of MMP 1 to TIMP 1, rather than the levels of MMP 1 or TIMP 1 alone, may play a significant role in human skin

Expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic stellate cells during rat hepatic fibrosis and its intervention by IL-10

AIM: To investigate the expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10).METHODS: Hepatic fibrosis was induced by CCl4administration and 60 male Sprague-Dawley rats were randomly divided into normal control group (group N, 8rats), CCl4-induced group (group C, 28 rats) and IL-10-treated group (group I, 24 rats). At the beginning of the 7th and 11th wk, rats in each group were routinely perfused with pronase E and type Ⅳ collagenase through portal vein catheter and the suspension was centrifuged by 11%Nycodenz density gradient to isolate hepatic stellate cells (HSCs). RT-PCR was used to analyze mRNA of MMP-2 and TIMP-1 from freshly isolated cells. Densitometric data were standardized with β-actin signals. Immunocytochemistry was performed to detect MMP-2 and TIMP-1 expression in HSC cultured for 72 h.RESULTS: Compared to group N in the 7th wk, MMP-2and TIMP-1 mRNA increased in group C (P= 0.001/0.001)and group I (P = 0.001/0.009). The level of MMP-2 and TIMP-1 mRNA in group I was significantly lower than that in group C (P= 0.001/0.001). In the 11th wk, MMP-2 mRNAin group I was still lower than that in group C (P = 0.005),but both dropped compared with that in the 7th week (P = 0.001/0.004). TIMP-1 mRNA in group I was still lower than that in group C (P= 0.001), and increased in group C (P = 0.001) while decreased in group I (P = 0.042)compared with that in the 7th wk. Same results were found by immunocytochemistry.CONCLUSION: Expression of MMP-2 and TIMP-1 is increased in hepatic fibrosis. IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression.

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in early focal cerebral infarction following urokinase thrombolysis in rats

Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion,and is associated with cerebral microvascular permeability,blood-brain barrier destruction,inflammatory cell infiltration and brain edema.Matrix metalloproteinase-9 also likely participates in thrombolysis.A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery.At 3 hours following model induction,urokinase was injected into the caudal vein.Decreased neurological severity score,reduced infarct volume,and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis.These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.

腹部创伤感染病人血清基质金属蛋白酶9、基质细胞衍生因子1表达及其诊断价值

目的 探究腹部创伤感染病人血清基质金属蛋白酶(MMP)-9、基质细胞衍生因子(SDF)-1表达及其诊断价值。方法 2021年7月~2022年7月收治的腹部创伤感染病人100例,作为病例组,同期腹部创伤未发生感染的病人100例为对照组。采用酶联免疫吸附法(ELISA)检测血清MMP-9、SDF-1水平;Spearman法分析血清MMP-9、SDF-1与SIRS评分和住院时间的相关性。ROC曲线分析血清MMP-9、SDF-1对腹部创伤感染病人的诊断价值。配对样本t检验分析腹部创伤感染病人治疗前后血清MMP-9、SDF-1水平。多因素Logistic回归分析影响腹部创伤感染发生的因素。结果 病例组病人血清MMP-9、SDF-1水平、C-反应蛋白(CRP)、白细胞计数(WBC)、血清中肿瘤坏死因子(TNF)-α、合并糖尿病、创伤类型等与对照组比较,差异有统计学意义(P<0.05)。腹部创伤感染病人血清MMP-9水平分别与SIRS评分、CRP、WBC、TNF-α呈正相关性(r=0.505、0.471、0.423、0.416,P<0.05);血清SDF-1水平分别与SIRS评分、CRP、WBC、TNF-α也呈正相关性(r=0.469、0.439、0.518、0.469,P<0.05)。ROC分析显示,血清MMP-9、SDF-1预测腹部创伤发生感染的曲线下面积(AUC)分别为0.850(95%CI:0.799~0.902)、0.806(95%CI:0.746~0.866),二者联合检测的AUC为0.914(95%CI:0.876~0.951),高于MMP-9、SDF-1单独检测(Z=1.987、2.97,P<0.05)。治疗后血清MMP-9、SDF-1表达水平低于治疗前,差异有统计学意义(P<0.05)。Logistic回归分析显示,合并糖尿病、创伤类型、血清MMP-9、SDF-1水平是腹部创伤病人感染的危险因素(P<0.05)。结论 腹部创伤感染病人血清MMP-9、SDF-1水平升高,二者可能参与腹部创伤感染的发生发展,对腹部创伤感染的诊断具有临床意义。

血清MMP-9、sTREM-1对输尿管结石患者术后泌尿系统感染的预测价值

目的探讨血清基质金属蛋白酶9(MMP-9)、可溶性髓系细胞触发受体-1(sTREM-1)对输尿管结石患者术后泌尿系统感染(UTI)的预测价值。方法选取2021年10月至2022年10月在该院泌尿外科收治的输尿管结石患者中术后发生UTI的68例患者(UTI组)和未发生UTI的68例患者(非UTI组)作为研究对象。采用酶联免疫吸附试验(ELISA)检测血清MMP-9、sTREM-1水平。采用Spearman法分析UTI组血清MMP-9、sTREM-1水平与临床资料的相关性,受试者工作特征曲线分析血清MMP-9、sTREM-1水平对输尿管结石患者术后UTI的预测价值,以及多因素Logistic回归分析输尿管结石患者术后UTI发生的影响因素。结果与非UTI组相比,UTI组血清MMP-9、sTREM-1水平显著升高,差异有统计学意义(P<0.05)。相关性分析发现,UTI组患者血清MMP-9和sTREM-1水平呈正相关(r=0.585,P<0.001)。二者联合预测输尿管结石患者术后UTI的曲线下面积(AUC)为0.961(95%CI:0.934~0.988),其灵敏度、特异度分别为73.36%和85.68%,二者联合预测的AUC高于MMP-9和sTREM-1单独预测的AUC(Z=25.420,P<0.001;Z=21.531,P<0.001)。MMP-9、sTREM-1水平是输尿管结石患者术后UTI发生的影响因素(P<0.05)。结论输尿管结石术后UTI患者血清MMP-9、sTREM-1水平升高,二者水平检测对输尿管结石患者术后UTI的发生具有重要预测价值。

术后血清MMP-2、SCCA1表达水平对鼻腔鼻窦内翻性乳头状瘤术后复发的预测价值

目的探讨术后血清基质金属蛋白酶-2(MMP-2)、鳞状细胞癌抗原1(SCCA1)表达水平对鼻腔鼻窦内翻性乳头状瘤(SNIP)患者术后复发的预测价值。方法回顾性分析手术治疗的SNIP患者65例,根据术后2年内复发情况,将其分为复发组(n=12)和未复发组(n=53)。Elisa法检测手术前后血清MMP-2、SCCA1表达水平。收录临床资料,包括性别、年龄、饮酒史、吸烟史、肿瘤部位、手术方式、术后有无应用5-氟尿嘧啶(5-Fluorouracil,5-FU)、Krouse分期及有无糖尿病、高血压;Logistic回归分析影响SNIP患者术后复发的危险因素;ROC曲线分析术后血清MMP-2、SCCA1表达水平对SNIP患者术后复发的预测价值。结果术后,2组血清MMP-2、SCCA1表达水平均较术前降低(P<0.05),但复发组血清MMP-2、SCCA1表达水平均高于未复发组(P<0.05)。Logistic回归分析显示,有吸烟史、术后未应用5-FU、Krouse分期为T3~T4期、术后血清MMP-2表达水平、SCCA1表达水平是影响SNIP患者术后复发的危险因素(P<0.05)。ROC曲线分析显示,术后血清MMP-2、SCCA1表达水平单独及二者联合预测SNIP患者术后复发的曲线下面积(AUC)分别为0.786、0.800、0.836,敏感度分别为83.33%、75.00%、91.67%,特异度分别为71.70%、79.25%、75.47%。结论术后血清MMP-2、SCCA1表达水平可作为预测SNIP患者术后复发的辅助指标,且二者联合预测的效果更佳。